Serum sodium concentration and the progression of established chronic kidney disease.

This is a post-peer-review, pre-copyedit version of an article published in Journal of Nephrology. The final authenticated version is available online at: https://doi.org/10.1007/s40620-018-0541-zBACKGROUND: Higher serum sodium concentration has been reported to be a risk factor for the development of incident chronic kidney disease (CKD), but its relationship with the progression of established CKD has not been investigated. We hypothesised that increased serum sodium concentration is a risk factor for estimated glomerular filtration rate (eGFR) decline in CKD. METHODS: This was a retrospective cohort study using data collected over a 6-year period, with baseline data obtained during the first 2 years. We included patients known to our renal service who had had a minimum of three blood tests every 2 years and an eGFR of < 60 mL/min/1.73 m2 at baseline. Exclusion criteria were renal replacement therapy, diabetes mellitus, heart failure and decompensated liver disease. A multiple linear regression model investigated the relationship between baseline serum sodium and eGFR decline after adjustment for confounding factors. RESULTS: 7418 blood results from 326 patients were included. There was no relationship between serum sodium concentration and estimated glomerular filtration rate at baseline. After multivariable adjustment, a 1 mmol/L increase in baseline serum sodium was associated with a 1.5 mL/min/1.73 m2 decline in eGFR during the study period (95% CI 0.9, 2.0). A reduction in eGFR was not associated with significant changes in serum sodium concentration over 6 years. CONCLUSION: Higher serum sodium concentration is associated with the progression of CKD, independently of other established risk factors. Conversely, significant alterations in serum sodium concentration do not occur with declining kidney function

Potential Deleterious Effects of Vasopressin in Chronic Kidney Disease and Particularly Autosomal Dominant Polycystic Kidney Disease

The antidiuretic hormone vasopressin is crucial for regulating free water clearance in normal physiology. However, it has also been hypothesized that vasopressin has deleterious effects on the kidney. Vasopressin is elevated in animals and patients with chronic kidney disease. Suppression of vasopressin activity reduces proteinuria, renal hypertrophy, glomerulosclerosis and tubulointerstitial fibrosis in animal models. The potential detrimental influence of vasopressin is probably mediated by its effects on mesangial cell proliferation, renin secretion, renal hemodynamics, and blood pressure. In this review, we discuss the increasing body of evidence pointing towards the contribution of vasopressin to chronic kidney disease progression in general and to autosomal dominant polycystic kidney disease in particular. These data allude to the possibility that interventions directed at lowering vasopressin activity, for example by the administration of vasopressin receptor antagonists or by drinking more water, may be beneficial in chronic kidney disease. Copyright (C) 2011 S. Karger AG, Base

Tolvaptan in patients with autosomal dominant polycystic kidney disease

Tolvaptan, as compared with placebo, slowed the increase in total kidney volume and the decline in kidney function over a 3-year period in patients with ADPKD but was associated with a higher discontinuation rate, owing to adverse events. (Funded by Otsuka Pharmaceuticals and Otsuka Pharmaceutical Development and Commercialization; TEMPO 3:4 ClinicalTrials.gov number, NCT00428948.)